|  |  |  | Endometrial Scratching group | Control group |  |  | |||
---|---|---|---|---|---|---|---|---|---|---|
Study | Inclusion criteria | Exclusion criteria | Type of embryo transfer | Method of endometrial injury | Timing of intervention | Instrument used | Control/ Type of intervention | Timing of intervention | Other interventions | Definitions of Pregnancy outcomes |
Karim Zadeh et al., (2008) [11] | Women that have undergone ART treatment cycles with at least 2 implantation failures | Not reported | Fresh ET | Single endometrial biopsy | Luteal phase of cycle preceding IVF | Novak curette | No intervention reported | NA | Not reported | Not reported |
Karimzadeh et al., (2009) [12] | Women 20-40 years old with RIF: 2-6 failed IVF-ET cycles and the transfer of >10 high grade embryos per patient without the achievement of clinical pregnancy | 1. Blood diseases 2. Poor responders in previous cycles defined as day 3 FSG:3 IU/ml or less than 4 follicles on the day of triggering 3. Uterine malformation 4. Endometrioma 5. Hydrosalpinx (U/S) | Fresh ET | Single endometrial biopsy | Day 21-26 of spontaneous cycle preceding IVF | Pipelle biopsy catheter (Pipelle de Cornier, Prodimed, Neuily-en-Thelle, France) | No intervention reported | NA | Not reported | Chemical pregnancy: measuring serum β-hCG level 14 days after ET (no threshold reported) Clinical pregnancy: intrauterine gestational sac with embryonic cardiac activity on TVS (timing of the assessment not reported) |
Karimzade et al., (2010) [13] | 1. Women< 38 years 2. BMI: >19 or <30 kg/m2 3. Day 3 FSH<12 IU/L 4. Triple layer endometrium with diameter more than 8 mm on the day of hCG administration 5. Normal ovarian response to COH defined as E2 on the day of hCG administration between 500 and 3,000 pg/mL and number of retrieved oocytes between 4 and 14 | 1. Uterine anomaly or pathology such as myoma and endometrial polyp 2. Endometriomas with a diameter >3 cm 3. Hydrosalpinges (TVS) | Fresh ET | Single endometrial biopsy; 2 small biopsies obtained from anterior and posterior walls of uterus with a Novak curette | Oocyte retrieval day (34–36 h after hCG administration) | Novak curette | No intervention reported | NA | ES and C: Prophylactic antibiotics (cefazolin 1 g IV) | Clinical pregnancy: gestational sac with embryonic cardiac activity (timing not reported) Ongoing pregnancy: pregnancy proceeding beyond 12 weeks of gestation |
Narvekar et al., (2010) [14] | Women≤37 years old with at least 1 previous failed fresh autologous IVF-ET/ICSI cycle with at least 4 good-quality embryos (grade I and II) | 1. Previous endometrial tuberculosis (including those treated with antituberculous treatment) 2. Intramural fibroids distorting the endometrial cavity/ submucous myomas/ Asherman’s syndrome 3. Hydrosalpinx | Fresh ET | Double endometrial biopsy; Pipelle introduced through the cervix, piston withdrawn, 360 degrees rotation, 4 up and down movements | Day of hysteroscopy 7-10 of cycle preceding IVF-ET Day 24-25 of cycle preceding IVF-ET | Pipelle biopsy catheter (Pipelle; Gynetics Medical Products, Hamont-Achel, Belgium) | No intervention reported | NA | ES and C: Doxycyclin 100 mg twice daily for 7 days after both the procedures Nonhormonal contraception in the cycle preceding IVF-ET ES: Diclofenac 50mg prior biopsy | Clinical pregnancy: embryonic cardiac activity in US (timing of assessment not reported) |
Safdarian et al., (2011) [15] | Women 20-39 years old (Patients with PCO not excluded) | 1. FSH>11 IU/L 2. Endometriosis 3. Hypothalamic amenorrhea 4. Azoospermic male | Fresh ET | Single endometrial biopsy | Day 21 of cycle preceding IVF-ET (use of contraceptive pill) | Pipelle biopsy catheter (Piplle-de Cornier, Prodimed, Neuilly-en-Thelle, France) | No intervention reported | NA | ES: Contraceptive pill before the IVF-ET treatment | Not reported |
Baum et al., (2012) [16] | 1. Women 18-41 years old 2. RIF: ≥3 failed IVF-ET cycles of good morphology embryos to a normal uterus, with good ovarian response in previous cycles 3. Women scheduled for IVF with fresh embryo transfer on the next cycle | 1. Uterine malformation 2. Endometrioma 3. Hydrosalpinx (U/S) | Fresh ET | Double endometrial biopsy | Day 9–12 and 21–24 of the spontaneous cycle preceding IVF | Pipelle biopsy catheter (Pipelle de Cornier; Prodimed, Neuillyen-Thelle, France) | Sham procedure; Biopsy catheter into the cervix without scraping | Day 9–12 and 21–24 of the spontaneous cycle preceding IVF | Not reported | Clinical pregnancy: intrauterine gestational sac with embryonic pole on U/S (timing of assessment not reported) |
Inal et al., (2012) [17] | Good responders to hormonal stimulation, who failed to conceive during ≥1 cycles of IVF/ET | 1. Hydrosalpinx 2. Thrombophilia 3. Submucous myoma 4. Other factors with negative impact on implantation | Fresh ET | Double endometrial biopsy; Pipelle introduced through the cervix, piston withdrawn, 3-4 times rotation in uterine cavity | Two biopsies with one-week interval during the luteal phase of the cycle preceding IVF | Pipelle biopsy catheter (Pipelle; de Cornier, Prodimed, Neuilly-en-Thelle, France) | No intervention reported | NA | ES: Antibiotics administered | Positive test: serum β-hCG>10 microIU/ml measured 12-14 days after the ET Clinical pregnancy: embryonic cardiac activity on US (timing of assessment not reported) Ongoing pregnancy: pregnancy reaching 12th gestational week |
Shohayeb et al., (2012) [18] | 1. Normal thin endometrium (<5 mm) on day 4 of menstruation 2. Women<39 years old 3. ≥2 previous failed IVF/ICSI cycles (RIF: Failure to achieve pregnancy after 2-6 ICSI cycles with the transfer of more than 10 high grade embryos) | 1. Submucous myoma distorting the endometrial cavity 2. Endometrial polyp distorting the endometrial cavity 3. Asherman's syndrome 4. Septate/ Bicornuate uterus (TVS or hysterosalpingography) | Fresh ET | Hysteroscopy and single endometrial biopsy regimen (S-EBR) | Day 4–7 of the cycle preceding IVF-ET | Novak curette | Sham procedure; Hysteroscopy without endometrial scraping | Day 4–7 of the cycle preceding IVF-ET | Not reported | Clinical pregnancy: intrauterine gestational sac with embryonic cardiac activity (timing of assessment not reported) |
Nastri et al., (2013) [19] | Women<38 years old who would be submitted to COS, oocyte retrieval and ET | Not reported | Fresh ET | Hysteroscopy and single endometrial biopsy; Pipelle introduced through the cervix, piston drawn back until self-locked, back and forth movements (2-4 cm) while rotating the sampler over the whole uterine cavity for 30 s. If pipelle suction orifice clogged before 30-s period, procedure restarted with another pipelle for another 30 s | 7–14 days before starting OS | Pipelle biopsy catheter (Pipelle de Cornier, Laboratoires Prodimed, Neully-En-Thelle, France) | Sham procedure; Drying the cervix with gauze for 30 s | 7–14 days before starting OS | ES and C: Oral contraceptives (ethinyl estradiol 30 mcg+levonorgestrel 150 mcg) since last menstruation, for at least 10 days before the appointment | Clinical pregnancy: at least one fetus with cardiac activity (timing of assessment not reported) Live birth: at least one liveborn baby Multiple pregnancy: presence of more than one fetus with cardiac activity Spontaneous miscarriage: loss of a clinical pregnancy before 20 completed weeks of gestation per clinical pregnancy |
Guven et al., (2014) [20] | 1. Women<35 years old 2. No previous IVF cycles and primary infertility 3. Normoresponders (antral follicle count of 5 to 10 in one ovary in early follicular phase) 4. Grade I or II embryos for transfer 5. Agreement to undergo endometrial biopsy during the COH cycle | 1. Endocrinopathies (including diabetes mellitus, hyperprolactinemia, Cushing’s disease and congenital adrenal hyperplasia) 2. Systemic diseases 3. Collagen disorders 4. Hypercholesterolaemia 5. Sickle cell anaemia 6. History of neoplasm 7. High risk for/ history of OHSS 8. Concurrent medication 9. Failure of follicle retrieval 10. Severe male infertility requiring TESA 11. Mullerian tract anomalies 12. History of endometrial instrumentation or surgery within 1 month of the study 1 3. Uterine factors (fibroids, polyps, adhesions) 14. Lack of agreement to undergo ES during the COH cycle | Fresh ET | Single endometrial biopsy; Scratching of anterior and posterior portions of the uterine cavity | Day 3 of the menstrual cycle following downregulation with leuprolide acetate | Biopsy catheter (Gynetics 4164 Probet Pipella; HD Aksu Medical, Ankara, Turkey) | No intervention reported | NA | None | Clinical pregnancy: gestational sac with embryonic cardiac activity on U/S, 4 weeks after ET |
Yeung et al., (2014) [21] | 1. Subfertile women indicated for IVF treatment 2. Normal uterine cavity demonstrated by saline infusion sonogram or hysteroscopy | 1. Endometrial polyp distorting the uterine cavity 2. Fibroid distorting the uterine cavity 3. Hydrosalpinx 4. IVF for PGD 5. Use of donor oocytes | Fresh ET | Hysteroscopy and single endometrial biopsy; Pipelle introduced through the cervix up to the uterine, piston withdrawn, back and forth movements between the fundus and internal os at least 3-4 times | 7 days after the LH surge in ovulatory women/ Day 21 of cycle immediately preceding IVF (anovulatory women) | Pipelle biopsy catheter (Pipelle de Cornier, Laboratoire C.C.D., France) | No intervention reported | NA | Not reported | Ongoing pregnancy: at least one embryonic cardiac activity on U/S beyond 20 weeks of gestation Clinical pregnancy: at least one gestational sac on U/S at 6 weeks of gestation Miscarriage: number of miscarriages before 20 weeks of gestation Multiple pregnancy: more than one gestational sac detected on U/S at 6 weeks of gestation |
Gibreel et al., (2015) [22] | Women aged<40 years with at least 1 previous failed IVF cycle | 1. Poor responders after previous IVF treatment 2. Endocrinopathy 3. Tubal disconnection for hydrosalpinx 4. History of endometrial curettage within 3 months of the study 5. Fibroids and other factors distorting the endometrial cavity (e.g., polyps or adhesions) | Fresh ET | Double endometrial biopsy; Pipelle introduced through the cervix up to the uterine fundus, then withdrawn for 1 cm, piston drawn back until self-locked. 2-3 back-and-forth movements | Day 21 and day 23-24 of the cycle preceding IVF | Pipelle biopsy catheter (Laboratoires Prodimed, Neully-En-Thelle, France) | Sham procedure; Introduction of a sound through the cervix, stopped just before crossing the internal OS | Day 21 and day 23-24 of the cycle preceding IVF | ES and C: Combined oral contraceptive pills from day 5 of the cycle preceding IVF | Live birth: delivery of one or more living fetuses after 24 weeks of gestation Clinical pregnancy: gestational sac with embryonic cardiac activity on U/S 4 weeks after ET |
Singh et al., (2015) [23] | 1. Women<35 years old with >1 previous failed IVF attempts 2. Good ovarian reserve (AFC>8, AMH: 2–6 ng/ml, FSH<8 IU/L) 3. No uterine manipulation within last 3 months (e.g., hysteroscopy, myomectomy) 4. Willingness to participate in the trial | 1. Women>35years old with confounding factors (e.g., poor ovarian reserve) 2. Grade III and IV endometriosis 3. History of septal resection or adhesiolysis 4. Uterine malformation 5. Other possible causes for failure of implantation (e.g., diabetes mellitus, hypertension, autoimmune diseases) | Fresh ET | Single endometrial injury; Karman’s cannula introduced through the cervix, anterior and posterior walls of endometrium scratched gently (4 mm) | Day 14-21 of cycle preceding IVF-ET | Karman's cannula | No intervention reported | NA | ES and C: Ciprofloxacin 500mg per os for 5 days | Not reported |
Xu et al., (2015) [24] | 1. Women<40 years old 2. FSH<10 IU/L 3. Failure of TEM to reach 7 mm by regular methods 4. No signs of submucosal uterine myoma, uterine malformations, endometrial polyps, or obvious IUA by TVS or diagnostic hysteroscopy 5. No signs of other diseases which could have affected endometrial growth 6. No contraindications for G-CSF treatment (e.g., chronic neutropenia, sickle cell disease, renal disease and history of malignancy) | Not reported | Frozen ET | Intrauterine G-CSF+single endometrial biopsy; Biopsy catheter introduced through the cervix until uterine fundus reached, piston withdrawn and the endometrium lightly scratched 1-2 times up and down on every wall of the uterine cavity, with abdominal US guidance. 300 g of G-CSF (100 g/0.6 ml) were injected into the cavity with the help of a 2-ml syringe and an embryo transfer catheter | On the day that one follicle became dominant-diameter: 12x12 mm | Endometrial biopsy catheter (Gynetics Medical Products N.V., Lommel, Belgium) | Intrauterine G-CSF; Under abdominal US guidance, 300 g of G-CSF (100 g/0.6 ml) were injected into the cavity with the help of a 2-ml syringe and an embryo transfer catheter | On the day that one follicle became dominant-diameter: 12x12 mm | ES: Intrauterine G-CSF after endometrial injury | Clinical pregnancy: gestational sac containing yolk sac on TVS, including ectopic pregnancy (timing of assessment not reported) Spontaneous abortion: loss of a clinical pregnancy of less than 20 weeks of gestation Implantation: gestational sacs on TVS, at least 4 weeks after ET |
Zhang et al., 2015 [25] | 1. RIF: 3 or more implantation failures in previous IVF/ICSI cycles 2. High-quality embryos subjected to cryopreservation by vitrification and still in good condition after being thawed | Not reported | Frozen ET | Hysteroscopy and single endometrial biopsy | Not reported | Digital camera (Tricam SLII, Germany, Carl Stortz, Tuttlingen, Germany) (Catheter used not reported) | No intervention reported | NA | ES: Hysteroscopy | Chemical pregnancy: β-hCG positive test (threshold not reported) Clinical pregnancy: At least 1 intrauterine gestational sac with embryonic cardiac activity (timing of assessment not reported) |
Aflatoonian et al., (2016) [26] | 1. Women <40 years old indicated for FET treatment 2. 1 or more frozen embryo(s) 3. Normal uterine cavity (TVS) | 1. History of endocrinopathies (hypothyroidism, diabetes mellitus) 2.Intrauterine abnormality (uterine polyp, submucosal fibroma, intrauterine adhesion) 3. Severe endometriosis (laparoscopy) 4. Endometrioma (U/S) | Frozen ET | Single endometrial biopsy; Pipelle introduced through the cervix up to uterine fundus, piston drawn back, sheath rotation and 2-3 back and forth movements | Day 21-23 of cycle preceding ET | Pipelle biopsy catheter (Endobiops, Prince Medical France) | No intervention reported | NA | Not reported | Chemical pregnancy: positive serum β-hCG test 14 days after ET Clinical pregnancy: gestational sac and embryonic cardiac activity on U/S 5 weeks after ET Ongoing pregnancy: embryonic cardiac activity on U/S beyond 12 weeks of gestation Miscarriage rate: loss of pregnancy <20 weeks of gestation |
Shahrokh-Tehraninejad et al., (2016) [27] | 1. Women<40 years old, 2. RIF: ≥2 previous failed IVF/ICSI cycles 3. ≥4 embryos with good quality (grade I) 4. Normal uterus in hysterosalpingography, sonography, hystrosonography or hysteroscopy 5. ≥7mm endometrium thickness at suppository progesterone administration day | 1. Submucousal, intramural and subserousal myoma>5 cm 2. Endometrioma≥3 cm 3. Hydrosalpinx 4. Bilateral obstruction of tube 5. <3-4 embryos 6. Endometrial tuberculosis or history of tuberculosis treatment 7. Asherman’s syndrome 8. BMI>30 kg/m2 9. Active vaginal or cervical infection 10. Systemic diseases (e.g., diabetes or systemic lupus erythematous) | Frozen ET | Single endometrial biopsy; Evaluation for LEI, endometrial injury in all 4 uterine walls by up and down movements of pipelle catheter in the uterine cavity | Day 21 of cycle preceding ET | Pipelle biopsy catheter | No intervention reported | NA | Not reported | Clinical pregnancy: intrauterine gestational sac on TVS during week 5 after ET |
Zygula et al., (2016) [28] | 1. Women< 40 years old with previous IVF failure | Not reported | Fresh ET | Single endometrial biopsy | Day 21 of cycle preceding IVF | Pipelle biopsy catheter | No intervention reported | NA | Not reported | Not reported |
Liu et al., (2017) [29] | 1. Infertile women indicated for IVF treatment 2. Women≤40 years old 3. Normal uterine cavity demonstrated by saline infusionsonogram 4. bFSH<12 IU/L | 1. Factors distorting the endometrial cavity (polyp, fibroid) 2. Hydrosalpinx 3. Endometriosis | Fresh ET | Single endometrial injury; Pipelle catheter introduced through the cervix up to the uterine fundus, piston drawn back, sheath rotation and back and forth movements within the uterine cavity | Proliferative phase group: day 10–12 of cycle preceding IVF Luteal phase group: 7–9 days after ovulation | Pipelle biopsy catheter (Shanghai Jiabao Medical Healthy Science Company, Shanghai, China) | Sham procedure- No endometrial scratching | Proliferative phase group: day 10–12 of cycle preceding IVF Luteal phase group: 7–9 days after ovulation | Not reported | Clinical pregnancy: intrauterine gestational sac and embryonic cardiac activity at 6 weeks of gestation Biochemical pregnancy: positive serum β-hCG (threshold not reported) |
Mak et al., (2017) [30] | All patients deemed suitable for natural-cycle FET and scheduled for FET cycles using non-donor oocytes, with normal ovulation | Uterine malformation or other pathology (e.g., polyps, endometriomas>4 cm, hydrosalpinx) | Frozen ET | Single endometrial biopsy; Pipette catheter introduced through the cervix, inner part of the device withdrawn, up and down movements approximately 2–3 cm within the uterine cavity. The procedure repeated at least 4 times with 360 degrees device rotation | Mid-luteal phase of cycle preceding ET (FET: 7±1 days after the surge of LH) | Biopsy catheter (Pipette; MedGyn, USA) | Sham procedure; Endocervical manipulation with sterile cotton wool stick inserted 2 cm into the cervical os, moved up and down and rotated 360° | Mid-luteal phase of cycle preceding ET (FET: 7±1 days after the surge of LH) | Not reported | Pregnancy: positive urine pregnancy test Clinical pregnancy: confirmed intrauterine gestational sac Ongoing pregnancy: at least one fetus with cardiac activity beyond 32 weeks of gestation Live birth: at least one live-born infant (minimum weeks of gestation not reported) |
Tk et al., (2017) [31] | 1. At least 1 previous failed IVF cycle with minimum of 2 good quality embryos (cleavage or blastocyst stage) transferred in an earlier attempt 2. Women≤38 years old 3. BMI≤29 kg/m2 4. FSH<10 IU/L | 1. Previous poor response (<3 oocytes retrieved in previous cycle) 2. Endometrial pathology 3. Uterine malformations 4. Severe endometriosis 5. Gross adenomyosis 6. Systemic diseases (e.g., autoimmune disorders) | Fresh ET | Double endometrial biopsy | Biopsy twice within 48h in the luteal phase of cycle preceding COH | Pipelle biopsy catheter | No intervention reported | NA | None | Biochemical pregnancy: β-hCG>5 mIU/ml level on day 18 after oocyte retrieval Clinical pregnancy: intrauterine gestational sac on U/S (timing of assessment not reported) Live birth: delivery of live fetus after 24 weeks of gestation Miscarriage: loss of pregnancy <24 weeks of gestation Multiple pregnancy: more than one gestational sac on early U/S Preterm delivery: delivery between 24 and 37 weeks of gestation |
Maged et al., (2018) [32] | 1. First ICSI cycle 2. Women< 40 years old 3. Day-3 FSH<10 IU/L 4. Normal serum prolactin 5. No uterine cavity abnormality | 1. Endocrinopathies (e.g., abnormal thyroid or adrenal function) 2. Ovarian cysts 3. Hydrosalpinx 4. Polyps 5. Azoospermia 6. ICSI for PGD | Fresh ET | Single endometrial biopsy; Pipelle catheter introduced through the internal os up to uterine fundus, piston withdrawn, sheath rotation and movements 3-4 times between fundus and inner os | Mid-luteal phase of the cycle immediately preceding IVF | Pipelle biopsy catheter (Cooper Surgical, Trumbull, CT, USA) | No intervention reported | NA | Not reported | Clinical pregnancy: embryonic cardiac activity within a gestational sac on U/S 4 weeks after ET Multiple pregnancy: multifetal pregnancy 4 weeks after ET Abortion: spontaneous abortion before 12 weeks of gestation |
Pecorino et al., (2018) [33] | 1. Women 25-37 years old with primitive or secondary infertility 2. At least 2 previous failed ICSI or FIVET (failed implantation) despite easy transfer and good quality embryos 3. Normal thickness and endometrial U/S pattern, defined as absence of intracavitary disease (fibroids, polyps, etc.), with no anamnestic severe deep endometriosis 4. Good quality of seminal fluid of partner and negative anamnesis for relevant diseases 5. Negative genetic, metabolic and infective evaluation | Not reported | Mixed | Single endometrial biopsy; Pipelle introduced through the cervix up to the uterine fundus, piston drawn back until self-locked, back and forth movements (3-4 cm) and then rotating movements over the whole uterine cavity for 30 s | Day 5-10 of cycle preceding IVF | Pipelle biopsy catheter (pipelle de Cornier® (Laboratoires PRODIMED, Neully-EnThelle, France) | Sham procedure; Embryo-transfer catheter inserted through the cervix in the uterine cavity | Day 5-10 of cycle preceding IVF | Not reported | Clinical pregnancy: intrauterine sac with embryonic cardiac activity on U/S (timing of assessment not reported) |
Sherif et al., (2018) [34] | 1. Age is between 25-30 years old. 2. BMI between 20 and 30 kg/m2 3. Cause of infertility: tubal causes, ovulatory causes, unexplained causes of infertility | 1. Women>30 years old 2. BMI>30 kg/m2 3. Endometriosis 4. Male factor infertility 5. Uterine malformations (U/S or HSG) 6. Previous failed ICSI 7. Hydrosalpinx and pyosalpinx (U/S) | Fresh ET | Single endometrial injury-modified COOK catheter movements on the posterior endometrium 1–2 cm from the fundus under U/S guidance | Day 6 of IVF-ICSI cycle | Modified COOK catheter | No intervention reported | NA | ES and C: Combined Oral Contraceptive from day 2 or day 3 of cycle preceding IVF for 21 days | Not reported |
Eskew et al., (2019) [35] | Women 18–43 years old undergoing a fresh or frozen embryo transfer | 1. Abnormal endometrial cavity evaluation 2. Third-party reproduction cycles | Mixed | Single endometrial biopsy; Cervix disinfection with an iodine solution, pipelle catheter introduced through the cervix to the fundus, plunger withdrawn, sheath rotation and 3-4 up and down movements, up to 2 passes | Patients OCP: during the last 7 days or up until 1 day after pills were discontinued (cycle preceding IVF-ET) Patients nOCP: Check for LH surge and ES 7–13 days following in the cycle preceding IVF-ET | Pipelle biopsy catheter (Endocell™ Trumbull, CT) | Sham procedure; Cervix disinfection with an iodine solution. Pipelle inserted into the posterior fornix and plunger withdrawn. Up and down movements of pipelle behind the cervix 3-4 times | Patients OCP: during the last 7 days or up until 1 day after pills were discontinued (cycle preceding IVF-ET) Patients nOCP: Check for LH surge and ES 7–13 days following in the cycle preceding IVF-ET | Not reported | Not reported |
Frantz et al., (2019) [36] | 1. 18–38 years old 2. 1 or no previous failed IVF cycle 3. Primary or secondary infertility 4. Regular menstrual cycles (between 27 and 32 days) 5. FSH ≤2 IU/L | 1. Participation to oocyte donation program 2. BMI>35 kg/m2 3. Hydrosalpinx 4. Uterine malformations 5. Fibroids (≥4 and the largest >5 cm) 6. Abnormal gynecological bleeding 7. Active vaginal infection 8. Pre-treatment with estrogen–progesterone or estradiol per os 9. Participation in another medically assisted reproduction study | Fresh ET | Single endometrial biopsy; Suction and rotation with a Pipelle catheter | Day 20-24 of cycle preceding IVF | Pipelle biopsy catheter (Pipelle de Cornier, CCD international, PROMIDED, Neuilly-en Thelle, France) | No intervention reported | NA | Not reported | Clinical pregnancy rate: at least one intrauterine gestational sac with embryonic cardiac activity Ongoing pregnancy: ≥12 weeks of gestation |
Gurgan et al., (2019) [37] | 1. Women<40 years old 2. RIF: failure to achieve clinical pregnancy after at least 4 good-quality embryos transferred in a minimum of 3 fresh or frozen cycles 3. FSH≤15 IU/L | 1. Congenital uterine malformations 2. Asherman's syndrome 3. Myoma or endometrial polyps distorting the endometrial cavity 4. Endometriosis or endometrioma 5. BMI<18.5 or >29.9 kg/m2 6. Endometrial thickness<7 mm in the cycle before ART | Mixed | Office hysteroscopy and single endometrial injury; Under sedation, 5 mm 30° lens supplied with a 5F working channel continuous flow office hysteroscope introduced through the cervix, endometrial injury with scissors first on the fundus by cutting transversally into the endometrium, then 3-4 vertical incisions 0.5 cm apart on the anterior and posterior walls of the uterus, 1-1.5 cm away from the fundus and with 1 cut for each lateral wall | Day 10-12 of cycle preceding IVF | 5 mm 30° lens supplied with a 5 F working channel continuous flow office hysteroscope (Bettocchi® Integrated Office Hysteroscope; KARL STORZ, Tuttlingen, Germany), scissors | No intervention reported | NA | None | Clinical pregnancy: at least one intrauterine gestational sac with embryonic cardiac activity on U/S (timing of assessment not reported) Early pregnancy loss: loss of an intrauterine pregnancy within the first trimester Premature birth: birth before 37 weeks of gestation |
Hilton et al., (2019) [38] | 1. 1 or no previous failed IVF cycle (women on their first or second IVF/ICSI cycle) 2. 18–39 years old 3. BMI 18–35 kg/m2 4. Evaluation of uterine cavity (hysterosalpingogram, sonohysterogram, hysteroscopy) performed in the preceding 24 months 5. Early follicular phase (day 2 or 3) serum FSH evaluated in the preceding 6 months 6. Use of a long GnRH agonist or GnRH antagonist protocol 7. Documented LH surge 9–11 days before enrolment for patients not pretreated with the oral contraceptive pill or use of the OCP for ≥ 10 days at the time of enrollment | 1. Previous participation in this study 2. Prior early follicular phase FSH≥12 IU/L 3. Previous poor ovarian response (IVF cycle canceled for poor response or ≤4 oocytes retrieved) 4. IVF for PGD or fertility preservation 5. Endocrinopathies (e.g., diabetes mellitus, uncontrolled thyroid disease) 6. Uterine malformations 7. Untreated hydrosalpinx 8. Contraindications to endometrial biopsy 9. Office hysteroscopy or other uterine procedure planned or performed during the cycle preceding IVF stimulation 10. Use of surgically retrieved sperm in this IVF cycle | Fresh ET | Single endometrial biopsy; No anesthesia. Pipelle catheter introduced through the cervix in the uterine cavity, inner core withdrawn, acquisition of endometrial tissue upon rotation within the cavity until sampling considered adequate for histological assessment by a local pathologist | 5–10 days preceding COS | Pipelle biopsy catheter | No intervention reported | NA | Not reported | Clinical pregnancy: documented embryonic cardiac activity 5 weeks after implantation Live birth delivery: deliveries that resulted in at least 1 live birth |
Women planning IVF with their own oocytes (stimulated IVF cycle with planned fresh-embryo transfer or frozen-embryo transfer with the use of stored embryos) | 1. ET not planned (e.g., fertility preservation or plan to freeze all embryos for storage) 2. Contraindications to pipelle biopsy (e.g., vaginismus) 3. Intrauterine procedures within 3 months before the start of IVF (hysteroscopy, sonohysterography, hysterosalpingography, laparoscopy, surgically managed miscarriage or endometrial biopsy) | Mixed | Single endometrial biopsy; Obtaining of endometrial biopsy sample with pipelle, according to clinic protocols. If inserting the pipelle in the uterus not possible, local anesthetic and cervical dilatation permitted or second attempt scheduled for another day or with a different clinician (or both). (Procedure discontinued at the participant’s request or due to clinician's inability to pass the pipelle) | Between day 3 of the cycle preceding ET and day 3 of the ET cycle | Pipelle biopsy catheter 3 mm in diameter (e.g., Pipelle de Cornier, Laboratoire CCD, France) | No intervention reported | NA | ES: Advice to take pain medication before the procedure | Biochemical pregnancy: positive pregnancy test (timing of assessment not reported) Multiple pregnancy: more than one sac with embryonic cardiac activity by any scan on approximately 6 weeks of gestation Miscarriages: losses of clinical pregnancy before 20 weeks of gestation, excluding ectopic pregnancy Stillbirths: losses of clinical pregnancy at or after 20 weeks of gestation (not including loss of one fetus in multiple pregnancies) Terminations: losses of an intrauterine pregnancy, through intervention by medical, surgical or unspecified means | |
Olesen et al., (2019) [39] | 1. IVF or ICSI patients with 1 or more prior implantation failures, despite top-quality embryo or blastocyst transfer(s) 2. Regular menstrual cycle (28–32 days) 3. 18–40 years old 4. BMI: 18–32 kg/m2 | 1. Congenital uterine malformations 2. Fibroids 3. Polyps 4. Hydrosalpinges 5. Adenomyosis | Fresh ET | Single endometrial biopsy; Patient lying in a lithotomy position and scratching performed once in each quadrant of the endometrium with a pipelle catheter | Day 18–22 of cycle preceding IVF | Pipelle biopsy catheter (Pipelle de Cornier (Laboratoires Prodimed) | No intervention reported | NA | Not reported | Not reported |
Berntsen et al., (2020) [40] | Women were 18-40 years old with at least 1 previous failed IVF/ICSI cycle (No criteria for ovarian reserve, no age criteria or other criteria for the male partner or male partner sperm) | 1. Freeze-all cycles/ frozen embryo transfers 2. BMI≥35 kg/m2 3. Intrauterine pathology as cause of infertility 4. Significant systemic disorders 5. Ongoing reproductive tract or systemic infection 6. Intrauterine abnormalities diagnosed during trial hysteroscopy 7. Spontaneous pregnancy during the trial | Fresh ET | Office hysteroscopy and single endometrial biopsy; No sedation, unless procedure not possible without local anesthetics. Office hysteroscopy with an evaluation of the uterine cavity and cervical canal the help of hysteroscope and saline as distension media. 1 or 2 biopsies primarily performed on the posterior wall of the uterus (no firm strategy for precise location) | Follicular phase of the cycle preceding IVF | ALPHASCOPETM hysteroscope (GMS40A) 1.9 mm with GYNECARE VERSASCOPETM sheath (GMS805) 3.5 mm (Ethicon, Johnson & Johnson, Livingston, Scotland), 7 F forceps (GIMMI1 GmbH) | No intervention reported | NA | ES: Oral paracetamol 1000 mg and Ibuprofen 400 mg one hour before hysteroscopy | Positive pregnancy test rates: serum β-hCG>10 IU/l on day 13–15 after ET Ongoing pregnancy: at least one intrauterine gestational sac with embryonic cardiac activity at gestational weeks 7-9 Live birth: delivery of a live fetus after 22 weeks of gestation |
Izquierdo Rodriguez et al., (2020) [41] | 1. 18-50 years old 2. Normal uterine cavity (2D TVS) 3. Patients with endometrial polyps if polypectomy was performed at least 2 months before the treatment cycle | 1. Low sperm quality 2. Uterine intervention within 1 month of the study 3. Uterine malformations (fibroids 0–2 FIGO stage, Müllerian malformations, severe adenomyosis) 4. Unilateral or bilateral hydrosalpinx 5. BMI>35 kg/m2 6. Frozen ET | Fresh ET | Single endometrial biopsy; Cervix disinfection with an iodine solution, biopsy catheter inserted through the cervix up to the uterine with abdominal U/S guidance, piston partially removed, back and forth movements and rotation 360 degrees of the catheter in order to scratch the four walls | 5 to 10 days before start of period and the endometrial preparation | Pipelle biopsy catheter (Pipelle de Cornier, Laboratoire CCD, France) | No intervention reported | NA | Not reported | Clinical pregnancy: intrauterine gestational sac on TVS at approximately 6 weeks of gestation Pregnancy: positive pregnancy test (serum β-hCG>10 mUI/ml) Ongoing pregnancy: pregnancy continued beyond 12 weeks Early miscarriage: clinical pregnancy lost before 12 weeks Late miscarriage: pregnancy stopped between the 12- 24 weeks of pregnancy Live birth: birth of a live baby beyond the 24 weeks of pregnancy |
Mackens et al. (2020) [42] | 1. Women 18-40 years old 2. Fresh ART cycle 3. GnRH antagonist down-regulation 4. Signed informed consent | 1. Reasons for impaired implantation (e.g., hydrosalpinx, fibroid distorting the endometrial cavity, Asherman’s syndrome, thrombophilia or endometrial tuberculosis) 2. Oocyte donation 3. Frozen ET 4. Embryos planned to undergo embryo biopsy 5. BMI>35 or <18 kg/m2 6. Participation in another study on medically assisted procreation during the same cycle 7. Previous participation in the study 8. Inability to comprehend the investigational nature of the proposed study | Fresh ET | Single endometrial biopsy; Pipelle introduced in the uterus until slight resistance from the fundus, piston withdrawn and 360 degrees device rotation as it was moved up and down 4 times | Day 6-8 of cycle of OS | Pipelle biopsy catheter (Pipelle de Cornier® Laboratoire CCD, France) | No intervention reported | NA | Not reported | Clinical pregnancy: intrauterine gestational sac on TVS at 7 weeks of gestation Cumulative reproductive outcomes: number of biochemical pregnancies, clinical pregnancies, early pregnancy losses and live births, taking into account all conceptions (spontaneous or following ART) within an actively monitored 6-month follow-up period following randomization |
Tang et al., (2020) [43] | 1. Patients indicated for frozen–thawed ET 2. Serum progesterone level< 1.2 ng/mL on the third day of the menstrual cycle 3. At least 2 or more previous implantation failures 4. Normal morphology of uterine cavity | 1. Pelvic surgery history 2. Difficult ET 3. Intrauterine malformations (severe adhesions, polyp, submucosal fibroid) 4.BMI>27 kg/m2 5. Hydrosalpinx 6. Endometriosis 7. Oral contraception drugs recently | Frozen ET | Single endometrial biopsy; Pipelle introduced through the cervix up to the uterine cavity, piston withdrawn and rotation 360 degrees and up and down movements 4 times Sample examined under microscope to evaluate the size and level of the injury and to verify the proliferative state of endometrium | Day 3 of the cycle preceding ET | Pipelle biopsy catheter (Beijing Saipu Jiuzhou Science and Technology Developent Company) | No intervention reported | NA | Not reported | Clinical pregnancy: gestational sac on TVS approximately 5 weeks after ET Biochemical pregnancy: positive β-hCG test 14 days after ET (threshold not reported) Miscarriage rate: loss of pregnancy before 20 weeks |
1. Women with at least 1 full IVF/ ICSI cycle with at least 1 embryo transfer without achieving a clinical pregnancy and planning a new fresh IVF/ICSI cycle 2. Regular indication for IVF/ICSI 3. 18–44 years old 4. Primary or secondary infertility 5. Normal TVS | 1. Grade III and IV endometriosis 2. Untreated uni- or bilateral hydrosalpinx 3. Previous endometrial scratching 3. Untreated endocrinopathies 4. Intermenstrual blood loss 5. Previous Caesarean section with niche-formation and intracavitary fluid on US 6. Increased risk of intra-abdominal infection 7. Oocyte donation 8. PGT | Fresh ET | Single endometrial biopsy- performed by suction | Mid-luteal phase. LH surge (+5–8 days), 5–10 days before the expected next menstruation or expected withdrawal bleeding (when taking oral contraceptives) | Biopsy catheter | No intervention reported | NA | Not reported | Clinical pregnancy: intrauterine gestational sac visible on U/S at 6–7 weeks of gestation Ongoing pregnancy: embryonic cardiac activity on U/S at 10 weeks of gestation Live birth: delivery of at least 1 live fetus after 24 weeks of gestation Multiple pregnancy: birth of multiple live fetuses after 24 weeks of gestation Live birth: ongoing pregnancy leading to live birth | |
Metwally et al., (2021) [44] | 1. Women 18–37 years old undergoing their first cycle of IVF, with or without ICSI, expected to be using fresh embryos and a single embryo transfer (SET) 2. Regular ovulatory menstrual cycle defined by clinical judgement or with ovulatory levels of midluteal serum progesterone, normal uterine cavity assessed by TVS at screening 3. No endometrial abnormalities that would require treatment to facilitate pregnancy (e.g., suspected intrauterine adhesions, uterine septae, submucosal fibroids or intramural fibroids >4 cm in diameter) 4. Good ovarian reserve assessed clinically, biochemically (FSH<10 UI/L) and normal follicular phase estradiol levels and/or normal AMH levels or sonographically (antral follicle count) 5. No history of previous radiotherapy or chemotherapy 6. No relevant vaginal/ uterine infections 7. (If randomized) Willingness to use a barrier method of contraception prior to the procedure if necessary | 1. Previous trauma to the endometrium (resection of uterine septum, intrauterine adhesions, or recent resection of significant submucous fibroids) 2. BMI≥35 kg/m2 3. Participating in another interventional fertility study 4. Grade IV endometriosis 5. Participants undergoing ultra-long protocols 6. Other endometrial procedures (e.g., endometrial biopsy for the collection of natural killer cells) | Fresh ET | Single endometrial biopsy; Speculum inserted into the vagina, cervix exposed and cleaned. Pipelle sampler or similar device inserted into the cavity of the uterus and plunger withdrawn, sampler rotated and withdrawn 3-4 times so that tissue appeared in the transparent tube | Mid-luteal phase of the cycle preceding IVF (defined as 5–7 days before the expected next period, or 7–9 days after a positive ovulation test) | Pipelle catheter or similar device | No intervention reported | NA | ES: Participants were required to use a barrier method of contraception (if necessary) in the menstrual cycle in which the ES was performed | Implantation: positive serum β-hCG or by a positive urine pregnancy test on approximately day 14 following egg collection Clinical pregnancy: observation of viable intrauterine pregnancy with a positive heart pulsation seen on U/S at/after 8 weeks of gestation Miscarriage: spontaneous pregnancy loss, including pregnancy of unknown location prior to 24 weeks gestation, within the 10.5 month post egg collection follow-up period Ectopic pregnancy: pregnancy outside the normal uterine cavity Multiple birth: the birth of more than one living fetus after completed 24 weeks of gestation Preterm delivery: live birth after 24 weeks and before 37 weeks gestation within the 10.5 month post egg collection follow-up period Stillbirth: delivery of a stillborn fetus showing no signs of life after 24 weeks gestation within the 10.5 month post egg collection follow-up period |
Zahiri et al., (2021) [45] | 1. History of ICSI failure at least twice 2. Age<40 years old 3. FSH≤12 IU/L 4. Normal ultrasound assessment of uterus (including myometrium and endometrium) 5. Normal HSG or normal laparoscopy assessment | 1. Endometrial lesions in hysteroscopy (myoma, polyp, Asherman’s syndrome or Mullerian anomaly) 2. Unavailability of at least 2 embryos of good quality 3. OHSS 4. Serum progesterone >1.5-2 ng/mL 5. Diabetes mellitus, CRF, thyroid disorders, kidney or hepatic diseases 6. Smoking or being exposed to cigarette smoke for at least 3 months prior to the intervention 7. In the case of diagnosing any endometrial lesions, including polyps-fibroma-adhesion or Müllerian anomaly during the patient was excluded from the study | Fresh ET | Hysteroscopy and single endometrial biopsy; Scratching by a curette on four sides of the endometrium (anterior, posterior, and two lateral sides) | Luteal phase of cycle preceding IVF | Curette | Sham procedure-hysteroscopy without intervention | Luteal phase of cycle preceding IVF | Not reported | Abortion: loss of gestational products before 12 weeks of gestation |
Izquierdo et al., (2022) [46] | 1. 18-50 years old 2. Normal uterine cavity (2D TVS) 3. Patients with endometrial polyps if polypectomy was performed at least 2 months before the treatment cycle | 1. Low sperm quality 2. Uterine intervention within 1 month of the study 3. Uterine malformations (fibroids 0–2 FIGO stage, Müllerian malformations, severe adenomyosis) 4. Unilateral or bilateral hydrosalpinx 5. BMI>35 kg/m2 6. Frozen ET | Fresh ET | Single endometrial biopsy; Cervix disinfection with an iodine solution, biopsy catheter inserted through the cervix up to the uterine with abdominal US guidance, piston partially removed, back and forth movements and rotation 360 degrees of the catheter in order to scratch the four walls | 5 to 10 days before start of period and the endometrial preparation | Pipelle biopsy catheter (Pipelle de Cornier, Laboratoire CCD, France) | No intervention reported | NA | Not reported | RIF: patients with 2 or more previous failed implantations non-RIF: patients with a maximum of 1 previous failed ET |
Noori et al., (2022) [47] | 1. Women with primary infertility undergoing their first IVF procedure who had a BMI≤35 kg/m2 2. 20-40 years old 3. Normal uterine cavities in previous HSG or previous hysteroscopy 4. FSH≤12 IU/L | 1. Indices of uterine lesions (submucosal uterine leiomyomas or endometrial polyps) 2. History of moderate to severe pelvic endometriosis 3. Diagnosis of moderate to severe male factor infertility based on the WHO indices 4. History of tobacco use or alcohol consumption 5. Previous failed IVFs 6. Lack of proper embryo for transfer | Frozen ET | Single endometrial biopsy | Luteal phase of IVF cycle preceding ET | Pipelle curette | No intervention reported | NA | ES and C: Patients were advised to use Oral Contraceptive Pills from day 3 of cycle following oocyte retrieval or use barrier contraceptive | Chemical pregnancy: β-hCG positive test (threshold and timing of assessment not reported) Clinical pregnancy: At least 1 intrauterine gestational sac with embryonic cardiac activity (timing of assessment not reported) |
Turktekin et al., (2022) [48] | 1. Women scheduled for total embryo freezing due to the risk of OHSS 2. Patients were diagnosed with PCOS based on the revised Rotterdam criteria, two out of three: (1) oligo and/or anovulation, (2) clinical and/or biochemical hyperandrogenism, and (3) polycystic ovaries determined with U/S | 1. Women with Asherman’s syndrome, endometrial polyp, submucous fibroids, uterine septum or other congenital uterine anomalies, hydrosalpinx or endometrioma 2. History of hormonal medication or intrauterine contraception use within the past 12 months 3. History of habitual abortion 4. Endocrine disorders | Frozen ET | Single endometrial biopsy; While the patient still under anesthesia, Pipelle catheter introduced through the cervix up to the uterine fundus, piston withdrawn to create negative pressure, catheter pushed back and forth in the cavity and withdrawn. (Procedure was repeated until most of the cavity was injured) | Day of oocyte retrieval (after the retrieval) | Pipelle biopsy catheter | Sham procedure- Pipelle catheter advanced through the cervix to the fundus and then removed from the cavity, no injury made | Day of oocyte retrieval (after the retrieval) | ES: A single dose of antibiotic prophylaxis was administered to the participants before the procedure | Clinical pregnancy rate: evidence of a gestational sac, confirmed by ultrasound examination at week 4 after ET Live birth: delivery of a live fetus after 24 completed weeks of gestational age Serum β-hCG levels: measured in all patients on the 12th day of embryo transfer (threshold not reported) Miscarriage: loss of fetus before 20 weeks of gestation |